Silencing of MEG3 gene promoted anti-cancer activity and drug sensitivity in glioma

Abstract

Aberrant expression of MEG3 has been shown in various cancers. The purpose of this study is to evaluate the effect of MEG3 on glioma cells including U87MG and patient-derived primary tumors cells and compare with nonglial HUVEC cells. Cell viability, migration and chemo sensitivity was assayed. Apoptosis was evaluated in MEG3 overexpressing and MEG3 suppressed cells. MEG3 expression was compared in patient-derived tumor cells with respect to IDH1 mutation status and WHO-grades. Silencing of MEG3 inhibited cell proliferation and reduced cell migration while overexpression of MEG3 promoted cell proliferation in glioma cells. MEG3 inhibition improved chemo sensitivity of glioma cells to 5-fluorouracil(5FU) but not to navitoclax. Suppression of MEG3 gene in patient-derived oligodendroglioma cells also showed the same effect whereas glioblastoma cell proliferation and chemo sensitivity were not affected by MEG3 inhibition. Further, cell death mechanism of action was found as apoptosis. Although MEG3 is a widely known tumor suppressor gene and its loss is associated with several cancer types, here we reported that MEG3 inhibition can be used in drug sensitivity for improving efficiency of known chemotherapeutics. We propose that the level of MEG3 should be evaluated in treatment of different glioma subtypes that are resistant to effective drugs.